Welcome to the UPF Digital Repository

Aggregation is a context-dependent constraint on protein evolution

Show simple item record

dc.contributor.author Monti, Michele
dc.contributor.author Armaos, Alexandros, 1989-
dc.contributor.author Fantini, Marco
dc.contributor.author Pastore, Annalisa
dc.contributor.author Tartaglia, Gian Gaetano
dc.date.accessioned 2021-11-30T07:17:06Z
dc.date.available 2021-11-30T07:17:06Z
dc.date.issued 2021
dc.identifier.citation Monti M, Armaos A, Fantini M, Pastore A, Tartaglia GG. Aggregation is a context-dependent constraint on protein evolution. Front Mol Biosci. 2021;8:678115. DOI: 10.3389/fmolb.2021.678115
dc.identifier.issn 2296-889X
dc.identifier.uri http://hdl.handle.net/10230/49093
dc.description.abstract Solubility is a requirement for many cellular processes. Loss of solubility and aggregation can lead to the partial or complete abrogation of protein function. Thus, understanding the relationship between protein evolution and aggregation is an important goal. Here, we analysed two deep mutational scanning experiments to investigate the role of protein aggregation in molecular evolution. In one data set, mutants of a protein involved in RNA biogenesis and processing, human TAR DNA binding protein 43 (TDP-43), were expressed in S. cerevisiae. In the other data set, mutants of a bacterial enzyme that controls resistance to penicillins and cephalosporins, TEM-1 beta-lactamase, were expressed in E. coli under the selective pressure of an antibiotic treatment. We found that aggregation differentiates the effects of mutations in the two different cellular contexts. Specifically, aggregation was found to be associated with increased cell fitness in the case of TDP-43 mutations, as it protects the host from aberrant interactions. By contrast, in the case of TEM-1 beta-lactamase mutations, aggregation is linked to a decreased cell fitness due to inactivation of protein function. Our study shows that aggregation is an important context-dependent constraint of molecular evolution and opens up new avenues to investigate the role of aggregation in the cell.
dc.description.sponsorship The research leading to these results was supported by the Dementia Research Institute (REI 3556 and AlzUK) (ARUK-PG2019B-020), European Research Council (RIBOMYLOME 309545 and ASTRA 855923), the H2020 projects (IASIS 727658 and INFORE 25080), the Spanish Ministry of Economy and Competitiveness BFU 2017-86970-P as well as the collaboration with Peter St. George-Hyslop financed by the Wellcome Trust.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Frontiers
dc.relation.ispartof Front Mol Biosci. 2021;8:678115
dc.rights © 2021 Monti, Armaos, Fantini, Pastore and Tartaglia. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.title Aggregation is a context-dependent constraint on protein evolution
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.3389/fmolb.2021.678115
dc.subject.keyword Cellular fitness
dc.subject.keyword Computational model
dc.subject.keyword Deep scanning
dc.subject.keyword Evolution
dc.subject.keyword Protein aggregation
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/309545
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/855923
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/727658
dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/BFU2017-86970-P
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion


This item appears in the following Collection(s)

Show simple item record

Search DSpace

Advanced Search


My Account


Compliant to Partaking